Mortality in patients after a recent myocardial infarction - A randomized, placebo-controlled trial of azimilide using heart rate variability for risk stratification

Background - Depressed left ventricular function ( LVF) and low heart rate variability ( HRV) identify patients at risk of increased mortality after myocardial infarction ( MI). Azimilide, a novel class III antiarrhythmic drug, was investigated for its effects on mortality in patients with depressed LVF after recent MI and in a subpopulation of patients with low HRV. Methods and Results - A total of 3717 post- MI patients with depressed LVF were enrolled in this randomized, placebo- controlled, double- blind study of azimilide 100 mg on all- cause mortality. Placebo patients with low HRV had a significantly higher 1- year mortality than those with high HRV ( > 20 U; 15% versus 9.5%, P < 0.0005) despite nearly identical ejection fractions. No significant differences were observed between the 100- mg azimilide and placebo groups for all- cause mortality in either the " at- risk" patients identified by depressed LVF ( 12% versus 12%) or the subpopulation of " high- risk" patients identified by low HRV ( 14% versus 15%) or for total cardiac or arrhythmic mortality. Significantly fewer patients receiving azimilide developed atrial fibrillation than did patients receiving placebo ( 0.5% versus 1.2%, P < 0.04). The incidences of torsade de pointes and severe neutropenia ( absolute neutrophil count less than or equal to 500 cells/ mu L) were slightly higher in the azimilide group than in the placebo group ( 0.3% versus 0.1% for torsade de pointes and 0.9% versus 0.2% for severe neutropenia). Conclusions - Azimilide did not improve or worsen the mortality of patients after MI. Low HRV independently identified a subpopulation at high risk of mortality.